Cognitive load in tele-robotic surgery: a comparison of eye tracker designs.

PURPOSE: Eye gaze tracking and pupillometry are evolving areas within the field of tele-robotic surgery, particularly in the context of estimating cognitive load (CL). However, this is a recent field, and current solutions for gaze and pupil tracking in robotic surgery require assessment. Considering the necessity of stable pupillometry signals for reliable cognitive load estimation, we compare the accuracy of three eye trackers, including head and console-mounted designs. METHODS: We conducted a user study with the da Vinci Research Kit (dVRK), to compare the three designs. We collected eye tracking and dVRK video data while participants observed nine markers distributed over the dVRK screen. We compute and analyze pupil detection stability and gaze prediction accuracy for the three designs. RESULTS: Head-worn devices present better stability and accuracy of gaze prediction and pupil detection compared to console-mounted systems. Tracking stability along the field of view varies between trackers, with gaze predictions detected at invalid zones of the image with high confidence. CONCLUSION: While head-worn solutions show benefits in confidence and stability, our results demonstrate the need to improve eye tacker performance regarding pupil detection, stability, and gaze accuracy in tele-robotic scenarios.

Accelerated sonochemical fabrication of MIn2S4 (M = Zn, Mg, Ni, Co) for ultra-high photocatalytic hydrogen peroxide production.

Ternary metal sulfide (MIn2S4) by virtue of large extinction coefficient, suitable band gap and stability, has been proposed as a candidate for photocatalytic synthesis hydrogen peroxide (H2O2). However, MIn2S4 is conventionally synthesized by solvothermal method that is generally characterized by tedious operational steps and long reaction time. In this work, four sonoMIn2S4 (M = Zn, Mg, Ni, Co) were successfully prepared by sonochemical method within 2 h. These as-synthesized sonoMIn2S4 delivered much high-efficient photocatalytic H2O2 generation. Particularly, the sonoZnIn2S4 presented H2O2 production rate of 21295.5 µmol∙g-1∙h-1 in water/benzylalcohol system, which is 3.0 times that of ZnIn2S4 prepared by solvothermal method. The remarkably improved photocatalytic performance of sonoZnIn2S4 might be due to the multiple defects and fast electron-hole pair separation caused by ultrasound cavitation effect. Other metal sulfide photocatalysts with high performance were efficiently fabricated by facile sonochemical technology as well. The sonochemical method realized the rapid preparation of metal sulfide photocatalysts and efficient production of H2O2, which benefits to meet the United Nations Sustainable Development Goals (SDGs) including SDG-7 and SDG-12.

Using DNA-encoded libraries of fragments for hit discovery of challenging therapeutic targets.

INTRODUCTION: The effectiveness of Fragment-based drug design (FBDD) for targeting challenging therapeutic targets has been hindered by two factors: the small library size and the complexity of the fragment-to-hit optimization process. The DNA-encoded library (DEL) technology offers a compelling and robust high-throughput selection approach to potentially address these limitations. AREA COVERED: In this review, the authors propose the viewpoint that the DEL technology matches perfectly with the concept of FBDD to facilitate hit discovery. They begin by analyzing the technical limitations of FBDD from a medicinal chemistry perspective and explain why DEL may offer potential solutions to these limitations. Subsequently, they elaborate in detail on how the integration of DEL with FBDD works. In addition, they present case studies involving both de novo hit discovery and full ligand discovery, especially for challenging therapeutic targets harboring broad drug-target interfaces. EXPERT OPINION: The future of DEL-based fragment discovery may be promoted by both technical advances and application scopes. From the technical aspect, expanding the chemical diversity of DEL will be essential to achieve success in fragment-based drug discovery. From the application scope side, DEL-based fragment discovery holds promise for tackling a series of challenging targets.

Intraoperative gaze guidance with mixed reality.

Efficient communication and collaboration are essential in the operating room for successful and safe surgery. While many technologies are improving various aspects of surgery, communication between attending surgeons, residents, and surgical teams is still limited to verbal interactions that are prone to misunderstandings. Novel modes of communication can increase speed and accuracy, and transform operating rooms. A mixed reality (MR) based gaze sharing application on Microsoft HoloLens 2 headset that can help expert surgeons indicate specific regions, communicate with decreased verbal effort, and guide novices throughout an operation is presented. The utility of the application is tested with a user study of endoscopic kidney stone localization completed by urology experts and novice surgeons. Improvement is observed in the NASA task load index surveys (up to 25.23%), in the success rate of the task (6.98% increase in localized stone percentage), and in gaze analyses (up to 31.99%). The proposed application shows promise in both operating room applications and surgical training tasks.

Effect of Tb3+ and Ce3+ Co-doping on the Structure and Photoluminescence Properties of Hexagonal Boron Nitride Phosphors.

In the paper, we have successfully prepared hexagonal boron nitride (h-BN:Tb3+, Ce3+) phosphors with melamine as the nitrogen source. The X-ray powder diffraction patterns confirm that the sample possesses a hexagonal crystal structure within the P 6 ¯ m2 space group. It is interesting that the co-doping combination of Tb3+ and Ce3+ can markedly enhance the threshold concentration of doped activators within the limited solid solution of h-BN phosphors. Under 302 nm excitation, the h-BN:Ce3+ phosphors exhibit broadband blue light emission at 406 nm. In h-BN:Tb3+, Ce3+ phosphors, the co-doping of Ce3+ not only ensures high phase purity but also results in strong green light emission. The energy transfer efficiency from Ce3+ to Tb3+ is about 55%. The fluorescence lifetime increases with the increase of Ce3+ and Tb3+ concentration, and the fluorescence lifetime of h-BN:0.025Tb3+, 0.05Ce3+ phosphor reached 2.087 ms. Additionally, the h-BN:0.025Tb3+, 0.05Ce3+ phosphor exhibits excellent thermal performance with an activation energy value of 0.2825 eV. Moreover, the photoluminescence quantum yield of the sample exceeds 52%. Therefore, the h-BN:Tb3+, Ce3+ samples can be used as green phosphors for solid state lighting and fluorescent labeling.

Protein-templated ligand discovery via the selection of DNA-encoded dynamic libraries.

DNA-encoded chemical libraries (DELs) have become a powerful technology platform in drug discovery. Dual-pharmacophore DELs display two sets of small molecules at the termini of DNA duplexes, thereby enabling the identification of synergistic binders against biological targets, and have been successfully applied in fragment-based ligand discovery and affinity maturation of known ligands. However, dual-pharmacophore DELs identify separate binders that require subsequent linking to obtain the full ligands, which is often challenging. Here we report a protein-templated DEL selection approach that can identify full ligand/inhibitor structures from DNA-encoded dynamic libraries (DEDLs) without the need for subsequent fragment linking. Our approach is based on dynamic DNA hybridization and target-templated in situ ligand synthesis, and it incorporates and encodes the linker structures in the library, along with the building blocks, to be sampled by the target protein. To demonstrate the performance of this method, 4.35-million- and 3.00-million-member DEDLs with different library architectures were prepared, and hit selection was achieved against four therapeutically relevant target proteins.

Synthesis of Diacylhydrazine Derivatives Based on Tetrazole-Focused DNA-Encoded Library.

Utilizing already existing DNA-encoded libraries (DELs) for the generation of a distinct DEL represents an expedited strategy for expanding the chemical space. Herein, we leverage the unique photoreactivity of tetrazoles to synthesize diacylhydrazines on DNA. Widely available carboxylic acids serving as building blocks were employed under the mild photomediated reaction conditions, affording diverse DNA-conjugated diacylhydrazines. This methodology also demonstrates robustness in DEL-compatible synthesis and facilitates the preparation of oligonucleotide-based chemical probes.

Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine.

Bioconjugation chemistry has emerged as a powerful tool for the modification of diverse biomolecules under mild conditions. Tetrazole, initially proposed as a bioorthogonal photoclick handle for 1,3-dipolar cyclization with alkenes, was later demonstrated to possess broader photoreactivity with carboxylic acids, serving as a versatile bioconjugation and photoaffinity labeling probe. In this study, we unexpectedly discovered and validated the photoreactivity between tetrazole and primary amine to afford a new 1,2,4-triazole cyclization product. Given the significance of functionalized N-heterocycles in medicinal chemistry, we successfully harnessed the serendipitously discovered reaction to synthesize both pharmacologically relevant DNA-encoded chemical libraries (DELs) and small molecule compounds bearing 1,2,4-triazole scaffolds. Furthermore, the mild reaction conditions and stable 1,2,4-triazole linkage found broad application in photoinduced bioconjugation scenarios, spanning from intramolecular peptide macrocyclization and templated DNA reaction cross-linking to intermolecular photoaffinity labeling of proteins. Triazole cross-linking products on lysine side chains were identified in tetrazole-labeled proteins, refining the comprehensive understanding of the photo-cross-linking profiles of tetrazole-based probes. Altogether, this tetrazole-amine bioconjugation expands the current bioconjugation toolbox and creates new possibilities at the interface of medicinal chemistry and chemical biology.

Association between metabolic dysfunction-associated fatty liver disease and abdominal aortic aneurysm.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is the second most common aortic pathological manifestation. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a wide impact on the cardiovascular system and may be a risk factor for AAA. The aim of this study was to investigate whether MAFLD is associated with the risk of AAA. METHODS AND RESULTS: We used data from the prospective UK Biobank cohort study. MAFLD is defined as hepatic steatosis plus metabolic abnormality, type 2 diabetes, or overweight/obesity. AAA is collected by ICD-10 code. Cox regression was established to analyze the association between MAFLD and AAA. A total of 370203 participants were included; the average age of the participants was 56.7 ± 8.0 years, and 134649 (36.4 %) were diagnosed with MAFLD. During the 12.5 years of follow-up, 1561 (0.4 %) participants developed AAA. After fully adjusting for confounding factors, individuals with MAFLD had a significantly increased risk of AAA (HR 1.521, 95 % CI 1.351-1.712, p < 0.001). Importantly, the risk of AAA increases with the severity of MAFLD as assessed by fibrosis scores. These associations were consistent according to sex, weight, and alcohol consumption but weaker in elderly or diabetics (P for interaction <0.05). The association between the MAFLD phenotype and AAA was independent of the polygenic risk score. Additionally, MAFLD was not associated with thoracic aortic aneurysm or aortic dissection events. CONCLUSIONS: There was a significant relationship between MAFLD and AAA. These findings strongly recommend early prevention of AAA by intervening in MAFLD.

Comparative Study of DNA Barcode Integrity Evaluation Approaches in the Early-Stage Development of DNA-Compatible Chemical Transformation.

DNA-encoded libraries (DEL) have emerged as an important drug discovery technical platform for target-based compound library selection. The success rate of DEL depends on both the chemical diversity of combinatorial libraries and the accuracy of DNA barcoding. Therefore, it is critical that the chemistry applied to library construction should efficiently transform on a wide range of substrates while preserving the integrity of DNA tags. Although several analytical methods have been developed to measure DNA damage caused by DEL chemical reactions, efficient and cost-effective evaluation criteria for DNA damage detection are still demanding. Herein, we set standards for evaluating the DNA compatibility of chemistry development at the laboratory level. Based on four typical DNA damage models of three different DEL formats, we evaluated the detection capabilities of four analytical methods, including ultraperformance liquid chromatography (UPLC-MS), electrophoresis, quantitative polymerase chain reaction (qPCR), and Sanger sequencing. This work systematically revealed the scope and capability of different analytical methods in assessing DNA damages caused by chemical transformation. Based on the results, we recommended UPLC-MS and qPCR as efficient methods for DNA barcode integrity analysis in the early-stage development of DNA-compatible chemistry. Meanwhile, we identified that Sanger sequencing was unreliable to assess DNA damage in this application.

Synthesis of Functionalized Triazoles on DNA via Azide-Acetonitrile "Click" Reaction.

Triazoles are privileged structural motifs that are embedded in a number of molecules with interesting biological activities. In this work, we developed a practical and general synthetic strategy to construct a medicinally important 5-amino-1,2,3-triazole moiety on DNA by coupling DNA-conjugated azides and monosubstituted acetonitriles via azide-acetonitrile "click" reaction. Under mild reaction conditions, this reaction displayed a broad substrate scope. Most substrates gave moderate-to-excellent conversions. Thus, this DNA-compatible reaction could be employed in practical DNA-encoded library (DEL) construction and potentially expand the chemical space of DNA-encoded libraries.

Attention-based deep clustering method for scRNA-seq cell type identification.

Single-cell sequencing (scRNA-seq) technology provides higher resolution of cellular differences than bulk RNA sequencing and reveals the heterogeneity in biological research. The analysis of scRNA-seq datasets is premised on the subpopulation assignment. When an appropriate reference is not available, such as specific marker genes and single-cell reference atlas, unsupervised clustering approaches become the predominant option. However, the inherent sparsity and high-dimensionality of scRNA-seq datasets pose specific analytical challenges to traditional clustering methods. Therefore, a various deep learning-based methods have been proposed to address these challenges. As each method improves partially, a comprehensive method needs to be proposed. In this article, we propose a novel scRNA-seq data clustering method named AttentionAE-sc (Attention fusion AutoEncoder for single-cell). Two different scRNA-seq clustering strategies are combined through an attention mechanism, that include zero-inflated negative binomial (ZINB)-based methods dealing with the impact of dropout events and graph autoencoder (GAE)-based methods relying on information from neighbors to guide the dimension reduction. Based on an iterative fusion between denoising and topological embeddings, AttentionAE-sc can easily acquire clustering-friendly cell representations that similar cells are closer in the hidden embedding. Compared with several state-of-art baseline methods, AttentionAE-sc demonstrated excellent clustering performance on 16 real scRNA-seq datasets without the need to specify the number of groups. Additionally, AttentionAE-sc learned improved cell representations and exhibited enhanced stability and robustness. Furthermore, AttentionAE-sc achieved remarkable identification in a breast cancer single-cell atlas dataset and provided valuable insights into the heterogeneity among different cell subtypes.

Association between cognitive impairment and risk of atrial fibrillation: The Atherosclerosis Risk in Communities study.

BACKGROUND: Atrial fibrillation (AF) is reportedly a risk factor for cognitive impairment. Interestingly, recent studies have emphasized that impaired cognition is probably an initiating factor of cardiovascular disease. Thus, we aimed to explore the association between impaired cognition and the risk of AF, and clarify the potential mechanisms. METHODS: Participants of visit 2 (1991-1993) in the Atherosclerosis Risk in Communities study were included. Global cognition z-scores and factor scores were calculated using the word fluency, delayed word recall, and digit symbol substitution tests. AF incidents were diagnosed by electrocardiography and inpatient records. The association of cognitive decline with AF risk and left atrial volume index (LAVI) was explored using Cox proportional hazards and linear regression models, respectively. RESULTS: During the median follow-up of 18.2 ± 6.2 years, 2056/11,675 (17.6%) participants developed AF. Participants in the lowest quartile of global cognition z- and factor scores had a higher risk of AF (hazard ratio [HR]: 1.271, 95% confidence interval [CI]: 1.094-1.477, p = 0.002; HR: 1.305, 95% CI: 1.110-1.535, p = 0.001, respectively) than those in the highest quartile. Global cognition z- and factor scores were negatively correlated with the LAVI (B: -0.411, 95% CI: -0.749 to -0.074, p = 0.017; B: -0.425, 95% CI: -0.833 to -0.017, p = 0.041, respectively). CONCLUSION: S: : Cognitive decline is significantly associated with a higher risk of AF, with atrial remodeling being a potential mechanism. Our results extend previous findings of the brain-heart axis and indicate the effects of cognitive injury on cardiac function and structure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT00005131.

Covalent Capture and Selection of DNA-Encoded Chemical Libraries via Photo-Activated Lysine-Selective Crosslinkers.

Covalent crosslinking probes have arisen as efficient toolkits to capture and elucidate biomolecular interaction networks. Exploiting the potential of crosslinking in DNA-encoded chemical library (DEL) selection methods significantly boosted bioactive ligand discovery in complex physiological contexts. Herein, we incorporated o-nitrobenzyl alcohol (o-NBA) as a photo-activated lysine-selective crosslinker into divergent DEL formats and achieved covalent capture of ligand-target interactions featuring improved crosslinking efficiency and site-specificity. In addition, covalent DEL selection was realized with the modularly designed o-NBA-functionalized mock libraries.

The Use of 810 and 1064 nm Lasers on Dental Implants: In Vitro Analysis of Temperature, Surface Alterations, and Biological Behavior in Human Gingival Fibroblasts.

Objective: The primary objective of this study was to evaluate the safety of 810 and 1064 nm laser treatment on dental implants. Background: Peri-implantitis is a challenge for clinicians and researchers. Methods: A pig mandible model was used to evaluate temperature increases during laser irradiation. Surface alterations on processed pure titanium discs were analyzed via scanning electron microscopy and measurement of surface contact angles. Processed titanium discs were cocultured in vitro with human gingival fibroblasts; subsequently, cell proliferation was measured. Results: The maximum temperature and time to reach each threshold were comparable. No surface alterations were detected after 810 nm laser irradiation, whereas surface cracks were observed after 1064 nm laser irradiation under the parameter setting of 31.84 W/cm2. Compared with unaltered processed pure titanium discs, the proliferation of human gingival fibroblasts was significantly greater on altered processed pure titanium discs. Conclusions: The use of either 810 or 1064 nm laser treatments may increase the risk of thermal damage in terms of increased temperature if the parameter setting is not warranted. In addition, the use of 1064 nm laser treatment could lead to changes in pure titanium discs that do not negatively affect cell proliferation. Further investigations of laser-assisted therapy are necessary to improve guidelines concerning the treatment of peri-implantitis. Clinical trial registration number: 2021-P2-098-01.

Sema3A Modified PDLSCs Exhibited Enhanced Osteogenic Capabilities and Stimulated Differentiation of Pre-Osteoblasts.

Genetically engineered stem cells, not only acting as vector delivering growth factors or cytokines but also exhibiting improved cell properties, are promising cells for periodontal tissue regeneration. Sema3A is a power secretory osteoprotective factor. In this study, we aimed to construct Sema3A modified periodontal ligament stem cells (PDLSCs) and evaluated their osteogenic capability and crosstalk with pre-osteoblasts MC3T3-E1. First, Sema3A modified PDLSCs was constructed using lentivirus infection system carrying Sema3A gene and the transduction efficiency was analyzed. The osteogenic differentiation and proliferation of Sema3A-PDLSCs was evaluated. Then, MC3T3-E1 was directly co-cultured with Sema3A-PDLSCs or cultured in condition medium of Sema3A-PDLSCs and the osteogenic ability of MC3T3-E1 was assessed. The results showed that Sema3A-PDLSCs expressed and secreted upregulated Sema3A protein, which confirmed successful construction of Sema3A modified PDLSCs. After osteogenic induction, Sema3A-PDLSCs expressed upregulated ALP, OCN, RUNX2, and SP7 mRNA, expressed higher ALP activity, and produced more mineralization nodes, compared with Vector-PDLSCs. Whereas, there was no obvious differences in proliferation between Sema3A-PDLSCs and Vector-PDLSCs. MC3T3-E1 expressed upregulated mRNA of ALP, OCN, RUNX2, and SP7 when directly co-cultured with Sema3A-PDLSCs than Vector-PDLSCs. MC3T3-E1 also expressed upregulated osteogenic markers, showed higher ALP activity, and produced more mineralization nodes when cultured using condition medium of Sema3A-PDLSCs instead of Vector-PDLSCs. In conclusion, our results indicated that Sema3A modified PDLSCs showed enhanced osteogenic capability, and also facilitated differentiation of pre-osteoblasts.

DNA-compatible combinatorial synthesis of functionalized 2-thiobenzazole scaffolds.

2-Thiobenzazole is among the privileged heterocyclic scaffolds in medicinal chemistry. Constructing such structural components in DNA-encoded libraries (DELs) may promote related bioactive hit discovery in a high-throughput fashion. Herein, we reported a DNA-compatible mild-condition synthetic methodology to efficiently forge functionalized 2-thiobenzazole scaffolds, realizing on-DNA sulfhydryl incorporation with broad substrate scope, thereby expanding the scope of 2-thiobenzazole-focused DNA-encoded chemical libraries.

DNA-Compatible Synthesis of Thiazolidione Derivatives via Three-Component Annulation and Knoevenagel Condensation.

Thiazolidione, conferring drug-like properties, is an important heterocycle that widely exists in medicinally relevant molecules. In this work, by efficiently assembling various DNA-tagged primary amines, abundant aryl isothiocyanates, and ethyl bromoacetate, we present a DNA-compatible three-component annulation to generate a 2-iminothiazolidin-4-one scaffold, which was further decorated via Knoevenagel condensation by employing (hetero)aryl and alkyl aldehydes. These thiazolidione derivatives should find broad use in focused DNA-encoded library construction.